Heart Rate-Lowering Efficacy and Respiratory Safety of Ivabradine in Patients with Obstructive Airway Disease: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

• Published in: American journal of cardiovascular drugs : drugs, devices, and other interventions devices, and other interventions, 2012-06, Vol.12 (3), p.179-188
• Main Authors: Majewski, Sebastian, Slomka, Sebastian, Zielinska-Wyderkiewicz, Ewa, Ciebiada, Maciej, Gorski, Pawel
• Format: Article
• Language: English
• Subjects: Cardiology; Medicine; Medicine & Public Health; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy
• ISSN: 1175-3277; 1179-187X
• DOI: 10.2165/11597400-000000000-00000

Background There is substantial evidence that heart rate (HR) is a powerful predictor of mortality in both normal individuals and in patients with cardiovascular disease. The use of b-adrenoceptor antagonists (β-blockers) has confirmed the importance of lowering elevated HR in a patient’s prognosis. However, these agents can have undesirable adverse effects (AEs) and due to the risk of bronchoconstriction are contraindicated in patients with obstructive airway disease. A selective bradycardic agent, without such undesirable effects, could be of therapeutic interest. Ivabradine, a new I f inhibitor that acts specifically on the sino-atrial node, is a pure HR-lowering agent. Objective The objective of this study was to assess HR-lowering efficacy and respiratory safety of ivabradine in patients with asthma and chronic obstructive pulmonary disease (COPD). Methods This was a randomized, single-center, double-blind, placebo-controlled, crossover trial. Enrolment began in May 2009, and the last patient completed the study in January 2011. The study was conducted in an ambulatory setting. A total of 40 patients completed the study (20 asthmatic patients and 20 COPD patients). Inclusion criteria were: documented diagnosis of asthma or COPD according to international guidelines, age 18–75 years, and mean HR on Holter ECG recording of ≥60 beats/min. Exclusion criteria included disease exacerbation in a previous month or inability to understand instructions on the study procedures. All patients received ivabradine 7.5 mg twice daily for 5 days and placebo twice daily for 5 days in a crossover manner, in one of the two arms of the study, with at least 2 days of washout between treatments. The main outcome measures included the difference in HR between ivabradine and placebo treatment and change in HR in comparison with baseline. Other evaluated outcomes were differences in the peak expiratory flow rate (PEFR), the daily symptom score, rescue medication consumption, and AEs. Results: Ivabradine produced significantly lower mean HR than placebo in both groups of patients: asthma 67.4 ± 8.38 versus 82.85±11.19 beats/min (p